Packaged systems for implanting markers in a patient and methods for manufacturing and using such systems

ABSTRACT

Packaged systems for implanting a marker in a patient and methods for manufacturing and using such systems. In one embodiment, a packaged system comprises an introducer having a cannula and a stylet configured to be received in the cannula, a marker in the cannula, and a package having a sterile compartment. The marker can have a casing configured to be implanted in a patient and a resonating circuit in the casing. The resonating circuit can comprise a coil configured to wirelessly transmit a target signal in response to a wirelessly transmitted excitation signal. The introducer is contained within the sterile compartment. In another embodiment, the marker is not loaded in the introducer within the compartment of the package.

TECHNICAL FIELD

The following disclosure relates generally to packaged systems forimplanting localization markers with wireless signal transmitters inpatients.

BACKGROUND

Medical procedures often require locating and treating target areaswithin a patient. Radiation therapy and many surgical procedures requirelocating the target with a high degree of precision to limit collateraldamage to healthy tissue around the target. It is particularly importantto know or estimate the precise location of the target in radiationoncology because it is desirable to limit the exposure of adjacent bodyparts to the radiation. In applications for treating prostate cancer,for example, the colon, bladder or other body parts of the patientadjacent to the prostate are desirably not impinged by thehigh-intensity radiation beam. Surgical applications, such as breastsurgery and other procedures involving soft tissue, also require knowingthe precise location of a target because a lesion is not necessarilyfixed relative to external landmarks on the patient.

Many imaging systems have been used to locate areas or particulartargets within a body before performing radiation oncology or surgicalprocedures. Although x-ray, Magnetic Resonance Imaging (MRI), CT, andother imaging techniques are useful to locate targets within the body atthe pre-operative stage of a procedure, they are often not suitable ordifficult to use in real time during surgery or radiation therapy. Forexample, the location of a lesion in soft tissue or an organ within thepatient's body may shift relative to external landmarks on the patientbetween the pre-operative imaging procedure and the actual radiation orsurgical procedure. Additionally, when imaging systems are used during aradiation or surgical procedure, they may not provide sufficientlyaccurate measurements of the location of the lesions and they mayinterfere with the radiation or surgical procedure. Therefore, imagingtechniques by themselves are not suitable for accurately identifying theactual location of a target for many medical applications.

Another technique to locate a target in a patient is to implant a markerrelative to the target. For example, implantable markers that generate asignal have been proposed for use to locate a selected target in apatient in radiation oncology procedures. U.S. Pat. No. 6,385,482 B1issued to Boksberger et al. (Boksberger) discloses a device having animplanted emitter unit located inside or as close as possible to atarget object and a plurality of receiver units that are located outsideof the patient. Boksberger discloses determining the location of thetarget object by energizing the emitter unit using a generator andsensing the signal from the emitter unit with the receiver units.Boksberger discloses and claims that the receiver units are configuredto determine the gradient of the magnetic field generated by the emitterunit. Boksberger discloses emitter units that are energized using awired connection to the external generator. Boksberger also indicatesthat it is conceivable to use an emitter unit that is energized by abattery or excited by an electromagnetic field generated by the externalgenerator. The wired emitter units disclosed in Boksberger, however, maynot be suitable for use in radiation oncology and many surgicalprocedures because it is impractical to leave a wired emitter unitimplanted in a patient for the period of time of such procedures (e.g.,five to forty days).

Another technique to locate a target in a patient is to implant passive,gold fiducials in or near the target site. The positions of the goldfiducials are determined periodically using radiation. Although goldfiducials are useful for localizing a target within a patient, thesesystems do not provide sufficiently accurate real time measurements ofthe target site location during radiation oncology procedures.

One practical difficulty of using wired markers or gold fiducials isimplanting the objects in the patient. Boksberger, for example,discloses positioning the emitter unit at a desired site in the body bypercutaneously inserting a hollow puncture needle into the patient andthen passing a tube through the hollow puncture needle. After the tubeis in place, Boksberger further discloses passing the emitter unitthrough the tube to position the emitter unit at or near the targetwithin the patient. This is a cumbersome process because a tube is leftin the patient during the radiation procedure to provide a passageway toremove the leads and the emitter unit. Moreover, the emitter units mustbe loaded into the tubes by skilled personnel at the healthcareprovider. Thus, implanting wire markers is cumbersome, inefficient, andnot well suited for radiation oncology applications that require apatient to return for treatments over a period of five to forty days.

Another process for percutaneously implanting objects in a patient isbrachytherapy for treating prostate cancer. In brachytherapy,radioactive sources or “seeds” are implanted relative to a tumor toprovide a high dose of radiation to the tumor, but not the healthytissue surrounding the tumor. FIGS. 1A and 1B are cross-sectional viewsof a two-piece introducer 100 of the prior art used in brachytherapy.Referring first to FIG. 1A, the introducer 100 includes a needle 102 anda stylet 104 slidably disposed within the needle 102. The stylet 104includes a first handle 101 and a blunt distal end 106. The needle 102includes a second handle 103 and a cannula 108 extending through thesecond handle 103. The cannula 108 is configured to hold radioactiveseeds 110 or other objects. The cannula 108 has a distal tip 105configured to percutaneously penetrate the patient for implantation ofthe seeds 110 in the patient. Inert spacers 111 can be used to providethe desired spacing between the seeds 110 when they are implanted in thepatient. The seeds 110 and spacers 111 are retained in the cannula 108by a plug 112 made from bone wax or other suitable bio-compatiblematerials.

To implant the desired arrangement of seeds 110 at a target location ina patient, an operator pushes the cannula 108 in a first direction(arrow A) to insert the tip 105 into the patient. The operator thenpushes the second handle 103 further in the first direction to positionthe tip 105 at the desired depth within the patient where the seeds 110are to be implanted. Throughout this motion, the operator moves theneedle 102 and the stylet 104 together as a unit. At the desired depth,the operator grasps the first handle 101 with one hand and the secondhandle 103 with the other hand. At this point, the operator attempts tohold the first handle 101 stationary while simultaneously sliding thesecond handle 103 back in a second direction (arrow B) toward the firsthandle 101. As shown in FIG. 1B, this movement causes the cannula 108 toslide over the seeds 110 and the spacers 111 to implant them in thepatient. In many situations, however, the operator moves the firsthandle 101 in the first direction (arrow A) while sliding the secondhandle 103 back in the second direction (arrow B). This causes thestylet 104 to push the seeds 110 out of the cannula 108, which can causethe seeds 110 to move laterally away from the axis of the cannula (i.e.,a “train wreck”). Thus, one concern of the prior art introducer 100 ismisplacement of the seeds 110.

Another concern of the prior art introducer 100 used in brachytherapyapplications is that a skilled operator typically loads a specificpattern of seeds and spacers into an introducer at the facility of ahealthcare provider according to the specific needs of each particularpatient. In most brachytherapy applications it is necessary to arrangethe seeds and spacers at the hospital or clinic according to thespecific parameters of each patient because the location and shape ofthe tumors vary among different patients. Arranging and loading theseeds for each patient is a time consuming process that requires skilledpersonnel and is subject to human error. Therefore, the techniques forinserting or implanting objects in the patients used in brachytherapyare not desirable in other applications.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are cross-sectional views of a two-piece introducer ofthe prior art used for implanting radioactive seeds in brachytherapy.

FIG. 2A is a cut-away isometric view of a packaged system for implantinga marker in a patient in accordance with one embodiment of theinvention.

FIG. 2B is a plan view showing a portion of the packaged system ingreater detail.

FIGS. 3A-3C are cross-sectional views illustrating the operation of anintroducer for use in the packaged system in accordance with anembodiment of the invention.

FIG. 4A is a cross-sectional view taken along a longitudinal axis of amarker for use in a packaged system in accordance with an embodiment ofthe invention.

FIG. 4B is a cross-sectional view in a plane 4B-4B normal to thelongitudinal axis of the marker shown in FIG. 4A.

FIG. 5 is a plan view of a packaged system for implanting a marker in apatient in accordance with another embodiment of the invention.

FIG. 6 is a plan view of a packaged system for implanting a marker in apatient in accordance with another embodiment of the invention.

FIG. 7 is a plan view of a packaged system for implanting a marker in apatient in accordance with another embodiment of the invention.

DETAILED DESCRIPTION

The following disclosure describes medical devices and methods relatedto packaged systems for implanting a marker in a patient. Certainspecific details are set forth in the following description and in FIGS.2A-7 to provide a thorough understanding of various embodiments of theinvention. It will be appreciated that other embodiments in accordancewith the invention can include additional or different features thanthose shown in 2A-7. Several other embodiments of packaged systems forimplanting a marker in a patient in accordance with the invention do notinclude some of the features shown in these figures. Additionally, forpurposes of clarity, like reference numbers refer to similar oridentical components.

FIG. 2A is a cut-away isometric view of a packaged system 200 forimplanting a marker in a patient. In this embodiment, the packagedsystem 200 includes an introducer 210 having a cannula 220 and a stylet222 configured to be received in the cannula 220. The packaged system200 can also include a marker 250 in the cannula 220. The marker 250 hasa casing configured to be implanted in a patient and a resonatingcircuit in the casing. The resonating circuit comprises a coilconfigured to wirelessly transmit a target signal in response to awirelessly transmitted excitation signal. The packaged system 200further includes a package 290 having a sterile compartment 292 in whichthe introducer 210 and the marker 250 are contained. In this embodiment,the package 290 is a sealed pouch or envelope, but it can be an enclosedtray or other structure in other embodiments. Several features of theintroducer 210 and the marker 250 will be described with reference toFIGS. 2A-4B.

The introducer 210 can include a handle 230 and an actuator assembly 300in the handle 230. The handle 230 has a proximal end 232 with a plug 234and a distal end 236 with an opening 238. The handle 230 can alsoinclude a longitudinal slot 235 along the top surface in which a button312 of the actuator assembly 300 can move. The handle 230 can alsoinclude notches 237 a and 237 b for receiving a tab 318 of the actuatorassembly 300. The interaction between the handle 230 and the actuatorassembly 300 is described in more detail below. The handle 230 also hasa cavity 239 for receiving a portion of the cannula 220 and a portion ofthe stylet 222.

The stylet 222 can have a proximal end positioned in the cavity 239 ofthe handle 230 and a distal end projecting out through the opening 238of the handle 230. In this embodiment, the proximal tip of the stylet222 is fixedly attached to the plug 234 so that the stylet 222 does notmove relative to the handle 230. The cannula 220 has a lumen thatreceives a portion of the stylet 222. In several embodiments, thecannula 220 is not fixedly attached to the handle 230. As such, thecannula 220 can not only slide over the stylet 222, but also through theopening 238 of the handle 230. The cannula 220 slides between a storageposition (shown in FIG. 2A) and a release position. The marker 250 iscontained within a distal portion 224 of the cannula 220 in the storageposition, but the marker 250 is expelled from the cannula 220 in therelease position. As such, at least a length of the distal portion 224of the cannula 220 slides over a distal tip 226 of the stylet 222 as themarker 250 is implanted in the patient.

FIG. 2B is a plan view illustrating one embodiment of the distal portion224 of the cannula 220 in greater detail. In this embodiment, the distalportion 224 has a beveled cutting edge 227 and a plurality ofprotrusions 228 a and 228 b projecting radially inwardly into a lumen229 of the cannula 220. The protrusions 228 a and 228 b arediametrically opposed across the lumen 229. In other embodiments, thecannula 220 can have only a single projection 228 on one side of thelumen 229. In either case, the protrusions are only slightly smallerthan the outside diameter of the marker 250. The protrusions providetactile feedback to the operator as the cannula 220 retracts over thestylet 222. Such tactile feedback provides an indication to the operatorthat the marker 250 has been released within the patient. This featurecan be particularly useful when the introducer 210 is used tosequentially implant a plurality of markers from the same introducer atdifferent depths or locations within the patient. Additionally, theprotrusions retain the marker 250 within the cannula 220 for shippingand storage. One advantage of the protrusions is that they are notsusceptible to fluctuations in temperatures so that the preloadedintroducers can be shipped and stored in hot environments.

FIGS. 3A-3C are cross-sectional views illustrating the interactionbetween the handle 230 and the actuator assembly 300 in the operation ofthe introducer 210. The actuator assembly 300 can include a slider 310that is fixedly attached to the cannula 220 and slidably received in thehandle 230. The slider 310, for example, can be an assembly includingthe button 312, the tab 318, and a flange 319. The button 312 isslidably received in the slot 235 of the handle 230 and the flange 319is fixed to a proximal end of the cannula 220. The tab 318 can bepositioned in the first notch 237 a of the handle 230 in the storageposition or the second notch 237 b of the handle 230 in the releaseposition.

FIG. 3A illustrates an initial stage of a method for implanting themarker 250 in a patient. At this stage an operator grips the handle 230to move the button 312 using a digit and inserts the cannula 220 intothe patient (arrow I). The operator then pushes the button 312 downwardto disengage the tab 318 from the first notch 237 a in the handle 230and slides the actuator assembly 300 in the proximal direction as shownin FIG. 3B (arrow R). The operator continues to move the slider 310proximally until the tab 318 engages the second notch 237 b to definethe release position as shown in FIG. 3C. The axial movement of theactuator assembly 300 moves the cannula 220 axially over the stylet 222because the cannula 220 is fixedly attached to the flange 319. Themarker 250 is implanted in the patient when the actuator assembly 300 isin the release position.

FIGS. 4A and 4B are cross-sectional views illustrating an embodiment ofthe marker 250 that can be loaded into the cannula 220 and packaged inthe package 290 in accordance with an embodiment of the invention. Themarker 250 can include a casing 251 formed from a bio-compatible barrierand configured to be implanted in the patient or otherwise attached tothe patient. The casing 251 can be a generally symmetrical capsule at asize to fit within a 14-gauge cannula for percutaneous implantation, butthe casing 251 can have other configurations and be larger or smaller.The casing 251, for example, can have barbs to anchor the casing 251 insoft tissue. In one embodiment, the casing 251 includes (a) a glasscapsule or shell 252 having a closed end 254 and an open end 256, and(b) a sealant 258 in the open end 256 of the shell 252. The casing 251and sealant 258 can be made from plastics, ceramics, glass or othersuitable bio-compatible materials.

The marker 250 can include a resonating circuit 260 in the casing 251.The resonating circuit 260 produces a wirelessly transmitted targetsignal in response to a wirelessly transmitted excitation signal. In oneembodiment, the resonating circuit 260 comprises a coil 262 having aplurality of windings of a conductor 264. The conductor 264 of theillustrated embodiment can be hot air or alcohol bonded wire having agauge of approximately 45-52 gauge. The coil 262 can have 800-2000turns, and the turns are preferably wound in a tightly layered coil.Many embodiments of the resonating circuit 260 also include a capacitor266 electrically coupled to the coil 262. The coil 262 by itself, or thecombination of the coil 262 and the capacitor 266, effect a signaltransmitter that resonates at the selected frequency. The signaltransmitter, for example, generates an alternating magnetic field at theselected resonant frequency in response to an excitation signal.

The resonating circuit 260 is powered by a wirelessly transmittedexcitation signal such that the resonating circuit is a leadless circuit(i.e., not connected to external lead wires that extend through orproject from the casing 251). In one embodiment, the excitation signalthat energizes the resonating circuit 260 is an alternating excitationmagnetic field generated externally with respect to the patient. Theexcitation signal can have a frequency that matches the resonantfrequency of the resonating circuit 260. In response to the excitationfield, the resonating circuit 260 produces a target signal or responsesignal that can be measured by a sensor array positioned externally withrespect to the patient. Suitable devices for generating the magneticexcitation field and sensing the target signal are disclosed in U.S.patent application Ser. Nos. 10/027,675 filed on Dec. 20, 2001;10/044,056 filed on Jan. 11, 2002; and 10/213,980 filed on Aug. 7, 2002,which are herein incorporated by reference.

The marker 251 further includes a ferromagnetic element 270 having afirst end 272 and a second end 274. The ferromagnetic element 270 is atleast partially surrounded by the coil 262. In the particular embodimentshown in FIG. 4A, the coil 262 surrounds the ferromagnetic element 270from the first end 272 to the second end 274. In other embodiments, thecoil 262 surrounds only a portion of the ferromagnetic element 270. Thecapacitor 266 can be positioned at the first end 272 of theferromagnetic element 270. Additionally, the resonating circuit 260 andthe ferromagnetic element 270 can be fixed to the casing 251 by anadhesive 276.

The ferromagnetic element 270 is preferably composed of ferrite or othermaterials that have high magnetic permeability compared to free space.The amount of energy that the inductor is capable of storing is limited,in part, by the magnetic field saturation of the ferromagnetic element270. Although it has been understood that the size of the ferromagneticmaterial should be maximized within the limited space of the marker, thevolume of the ferromagnetic element 270 in the particular embodiment ofthe marker 250 shown in FIG. 4A is significantly less than the availablevolume within the casing 251. The smaller volume of the ferromagneticelement 270 reduces the force exerted on the marker 251 when it isplaced in a magnetic resonance imaging device having a field strength of1.5 T including a corresponding gradient field of approximately 3 T/m.In one embodiment, the ferromagnetic element has a volume such that whenthe marker is in a magnetic resonance device, then the force exerted onthe marker by the magnetic field is less than gravitational forceexerted on the marker. Additionally, the small volume of theferromagnetic element 270 reduces the size of the artifact in an imagefrom a magnetic resonance device. It will be appreciated thatferromagnetic materials will produce an artifact (i.e., a region inwhich image information is suppressed) in an image produced by amagnetic resonance imaging device. The volume of the ferromagneticelement 270 can be reduced to a size such that it produces a smallartifact in an image from a magnetic resonance device. In general, suchferromagnetic elements 270 have small diameters less than the size ofcommercially available ferrite rods for transponder applications (i.e.,0.75 mm diameter ferrite rods available from Ferroxcube of Spain).

FIG. 4B is a cross-sectional view of the marker 251 taken along line4B-4B of FIG. 4A. In one embodiment, the ferromagnetic element 270 is aferrite rod having a diameter D₁ of approximately 0.20-0.70 mm, but theferromagnetic element 270 can have other cross-sectional configurationsin other embodiments. For example, an extruded ferrite rod can have anelliptical, oval or polygonal cross section. The ferromagnetic element270 can have a length of approximately 2.0-20 mm. In one particularembodiment the ferromagnetic element 270 has a diameter of approximately0.25-0.50 mm and a length of 2-12 mm, and in another embodiment theferromagnetic element 270 has a diameter of 0.30-0.35 mm and a length of4.0-6.0 mm. The coil 262 has an inner diameter of approximately0.20-0.80 mm and an outer diameter D₂ of approximately 0.6-1.4 mm or0.8-1.9 mm. The casing 251 can have an outer diameter D₃ ofapproximately 1.0-3.0 mm. In other embodiments, the coil 262 can havedifferent inner and outer diameters, and the casing 251 can have adifferent outer diameter. In another particular embodiment, the diameterD₁ of the ferromagnetic element 270 is approximately 0.30-0.50 mm, theinner diameter of the coil 262 is approximately 0.30-0.60 mm, the outerdiameter D₂ of the coil 262 is approximately 1.2-1.9 mm (or 1.2-1.4 mm),and the outer diameter D₃ of the casing 251 is approximately 1.8-2.0 mm.The volume of the ferromagnetic element 270 can be approximately0.35-19.0 mm³.

Referring back to FIG. 2, the packaged system 200 is useful for storingpreloaded introducers that contain resonating markers used to identifythe location of a target within a patient. In operation, a user can openthe package 290 and remove the preloaded introducer 210. The user thenpercutaneously inserts the cannula 220 and stylet 222 into the patientusing image guided techniques to locate the marker 250 at a desiredlocation within the patient. As explained above, the operator then movesthe actuator assembly 300 in a proximal direction to retract the cannula220 and release the marker 250 at the desired location within thepatient.

One advantage of the packaged system 200 is that the markers 250 arepreloaded in the introducer 210 and stored in a sterile compartment 292to provide a more efficient product to healthcare providers. The markerscan be preloaded in the introducer because this application is directedtoward markers that are energized by a wirelessly transmitted magneticfield and produce a wirelessly transmitted target signal. It is moredifficult to preload wired markers because the introducer mustaccommodate the external leads attached to the marker. Moreover, unlikebrachytherapy applications that require custom configuration of theseeds in an introducer, applications for using a wireless marker do notrequire a custom configuration of the marker relative to the introducer.As such, the aspect of preloading a marker in an introducer andpackaging the introducer in a sterile compartment is not useful forimplanting the objects of the prior art for use in their intendedpurposes.

The packaged system 200 illustrated in FIG. 2A can have severaldifferent embodiments. For example, a plurality of markers 250 can bepreloaded into the cannula 220, and the markers can have the samefrequency or the markers can have different frequencies. In anotherembodiment, the packaged system 200 can have a plurality of markers inthe cannula and spacers positioned between the markers. The spacersprovide a known linear distance between the markers to enhance theaccuracy with which the markers can be implanted in a patient. Otherembodiments of the packaged system 200 have a container including a traywith a retainer for holding the introducer and a cover sealed to thetray. Additionally, the stylet 222 can be inserted in the cannula 220 asshown in FIG. 2A, but in still other embodiments the stylet 222 isseparate from the cannula 220 within the package 290.

FIG. 5 is an isometric view of a packaged system 400 for implanting amarker in a patient in accordance with another embodiment of theinvention. In this embodiment, the packaged system 400 includes aplurality of introducers 410 (identified individually by referencenumbers 410 a-c) and a plurality of markers 450 (identified individuallyby reference numbers 450 a-c). A first marker 450 a is loaded in thefirst introducer 410 a, a second marker 450 b is loaded in the secondintroducer 410 b, and a third marker 450 c is loaded in the thirdintroducer 410 c. The introducers 410 a-c and the markers 450 a-c can besubstantially similar or identical to the introducer 210 and the marker250, respectively, described above with reference to FIG. 2A. A numberof additional items, such as a syringe 462, tweezers 464 and a swab 466can also be included in the packaged system 400.

The packaged system 400 further includes a package having a tray 490 anda cover 491 sealably attached to the tray to create a compartment 492.The tray 490 can further include a plurality of introducer retainers 493(identified individually by reference numbers 493 a-c) that retain theintroducers 410 a-c, respectively. The retainers 493 can be moldedprojections that grip the cannulas or the handles of the introducers410, or the retainers 493 can be depressions in the tray 490 or cover491 configured to conform to the contour of the introducers 410 a-c.

The introducers 410 can be loaded with markers that transmit differenttarget signals. For example, the first marker 450 a can be configured towirelessly transmit a first target signal at a first frequency inresponse to a first excitation signal; the second marker 450 b can beconfigured to wirelessly transmit a second target signal at a secondfrequency in response to a second excitation signal; and the thirdmarker 450 c can be configured to wirelessly transmit a third targetsignal at a third frequency in response to a third excitation signal.The markers 450 a-c can have the same frequency in other embodiments.

FIG. 6 is an isometric view illustrating another embodiment of thepackaged system 400. In this embodiment, the first introducer 410 a isloaded with a plurality of first markers 450 a, the second introducer410 b is loaded with a plurality of second markers 450 b, and the thirdintroducer 410 c is loaded with a plurality of third markers 450 c. Themarkers 450 a-c can be configured to transmit target signals havingdifferent frequencies as explained above with reference to FIG. 5. Inanother embodiment, one or more of the introducers 410 can include aspacer between two markers. Referring to the third introducer 410 c inFIG. 6, for example, a spacer 451 can be placed between one or more ofthe markers 450 c to provide a known lineal spacing between a group ofmarkers that is to be implanted relative to a target site in a patient.

FIG. 7 is an isometric view of a packaged system 500 in accordance withanother embodiment of the invention. In this embodiment, the packagedsystem 500 can include a plurality of the introducers 410 a-c and aplurality of the markers 450 a-d. The packaged system 500 is differentfrom the packaged system 400 in that the markers 450 are not preloadedinto the introducers 410. The packaged system 500 can include a tray 590and a cover 591 sealed to the tray to form a sealed, sterile compartment592. The tray 590 can have a plurality of retainers, such asdepressions, to hold the introducers 410 and the markers 450. Theretainers for the markers 450 can be small depressions that are shapedslightly larger than the markers. The markers 450 can include a firstset 602 of first markers 450 a, a second set 604 of second markers 450b, a third set 606 of third markers 450 c, and a fourth set 608 offourth markers 450 d. The first markers 450 a can wirelessly transmit afirst signal at a first frequency, the second markers 450 b canwirelessly transmit a second wireless signal at a second frequency, thethird markers 450 c can wirelessly transmit a third signal at a thirdfrequency, and the fourth markers 450 d can wirelessly transmit a fourthsignal at a fourth frequency. The packaged system 500 can have otherembodiments with a different number of introducers and markers. Forexample, the packaged system 500 can include only a single introducerand three unloaded markers that have different frequencies. As such, thepackaged system 500 is not limited to the particular configuration shownin FIG. 7.

The particular markers can include indicia, such as dots, colors, linesor text, that indicate the actual frequency or provide an indicator ofthe frequency. The indicia can be markings that are correlated with alegend 595 to determine the actual frequency X, Y, Z or Q of aparticular marker. In operation, the markers can be loaded into theintroducers after the cover 591 has been removed from the tray 590. Thepackaged system 500 accordingly requires the operator to perform theextra procedures of loading the markers into the introducers.

From the foregoing, it will be appreciated that although embodiments ofthe item matching system have been described for purposes ofillustration, various modifications may be made without deviating fromthe spirit and scope of the invention. Accordingly, the invention is notlimited except by the appended claims.

1-30. (canceled)
 31. In localization systems that involve implantingmarkers in a patent, a method for manufacturing a packaged system forimplanting a marker in a patient, comprising: providing a first markerhaving a first casing configured to be implanted in a patient and afirst resonating circuit in the first casing, wherein the firstresonating circuit comprises a first coil configured to wirelesslytransmit a first target signal in response to a wirelessly transmittedfirst excitation signal; preloading the first marker into a firstcannula of a first introducer; and sealing the first introducer with thefirst marker in the first cannula in a compartment of a package.
 32. Themethod of claim 31, further comprising: providing a second marker havinga second casing configured to be implanted in the patient and a secondresonating circuit in the second casing, wherein the second resonatingcircuit comprises a second coil configured to wirelessly transmit asecond target signal in response to a wirelessly transmitted secondexcitation signal; and preloading the second marker into the firstcannula of the first introducer before sealing the first introducer inthe compartment of the package.
 33. The method of claim 32 whereinproviding the first marker comprises configuring the first resonatingcircuit to have a first frequency, and providing the second markercomprises configuring the second resonating circuit to have a secondfrequency different than the first frequency.
 34. The method of claim 32wherein providing the first marker comprises configuring the firstresonating circuit to have a first frequency, and providing the secondmarker comprises configuring the second resonating circuit to have thefirst frequency.
 35. The method of claim 32, further comprising placinga spacer in the cannula between the first and second markers.
 36. Themethod of claim 31, further comprising: providing a second marker havinga second casing configured to be implanted in the patient and a secondresonating circuit in the second casing, wherein the second resonatingcircuit comprises a second coil configured to wirelessly transmit asecond target signal in response to a wirelessly transmitted secondexcitation signal; and preloading the second marker into a secondcannula of a second introducer; and sealing the second introducer in thecompartment of the package with the first introducer.
 37. The method ofclaim 36 wherein providing the first marker comprises configuring thefirst resonating circuit to have a first frequency, and providing thesecond marker comprises configuring the second resonating circuit tohave a second frequency different than the first frequency.
 38. Themethod of claim 36 wherein providing the first marker comprisesconfiguring the first resonating circuit to have a first frequency, andproviding the second marker comprises configuring the second resonatingcircuit to have the first frequency.
 39. The method of claim 36, furthercomprising placing a spacer in the cannula between the first and secondmarkers.
 40. In localization systems for determining the location of atarget site in a patient, a method for manufacturing and handling apackaged system for implanting a marker in the patient, comprising:providing a first marker having a first casing configured to beimplanted in a patient and a first resonating circuit in the firstcasing, wherein the first resonating circuit comprises a first coilconfigured to wirelessly transmit a first target signal in response to awirelessly transmitted first excitation signal; preloading the firstmarker into a first cannula of a first introducer; sealing the firstintroducer with the first marker in the first cannula in a compartmentof a package; and transporting the first introducer with the firstmarker in the first cannula in the compartment of the package to acustomer.